Pravastatin normalises peripheral cardiac sympathetic hyperactivity in the spontaneously hypertensive rat

Herring, Neil; Lee, Chee Wan; Sunderland, Nicholas; Wright, Kate; Paterson, David J.

doi:10.1016/j.yjmcc.2010.09.025

Cited by 36 publications

(41 citation statements)

References 36 publications

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“…This possibility was supported by our and other's studies, which indicated that the AT1 blocker, losartan, can inhibit prostate hyperplasia in SHRs [21,23]. A previous study has shown that statin can normalize sympathetic hyperactivity in SHR [24]. However, simvastatin failed to influence the Ang-II serum levels in the present experiment.…”

Section: Discussionsupporting

confidence: 81%

Influence and Pathophysiological Mechanisms of Simvastatin on Prostatic Hyperplasia in Spontaneously Hypertensive Rats

et al. 2013

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Objective: To explore the effects and mechanisms of simvastatin on prostate hyperplasia in spontaneously hypertensive rats (SHRs). Methods: Thirty-six male SHRs were randomly divided into three groups: the 10 and the 20 mg/kg/d simvastatin group and the control group. After 6 weeks the ultra-microscopic prostate structures were observed. The serum levels of interleukin-6 (IL-6), insulin-like growth factor (IGF-1) and angiotensin II (Ang-II) were measured by enzyme-linked immunosorbent assays. The endothelium-derived nitric oxide synthase (eNOS) expression was evaluated with immunohistochemistry. Results: Compared to the control group, the 20 mg/kg/d simvastatin group presented with lower absolute (p = 0.005) and relative prostate weight (p = 0.009). The basal cells and columnar cells presented with edema, condensed heterochromatin in interstitial fibroblast nuclei, widened nucleus gaps, and decreased mitochondria and endoplasmic reticulum in the 10 mg/kg/d simvastatin group, these changes were more pronounced in the 20 mg/kg/d simvastatin group. The IL-6 levels in the 10 and 20 mg/kg/d simvastatin groups were lower than those of the controls (p = 0.005 and p = 0.008). The IGF-1 levels of the 20 mg/kg/d simvastatin group were reduced compared to the control group (p = 0.016). Conclusions: Simvastatin can delay and inhibit prostatic hyperplasia and progression in SHR. These actions may be mediated through the suppression of inflammatory and growth factors.

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Section: Discussionsupporting

confidence: 81%

Influence and Pathophysiological Mechanisms of Simvastatin on Prostatic Hyperplasia in Spontaneously Hypertensive Rats

et al. 2013

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“…Experimental studies have shown that statins can influence sympathetic activity. 27 However, since statins had no effect on the risk of heart failure in the PROSPER trial during the study period, it seems unlikely that the association between heart rate and heart failure is influenced by statins. 14 Our study also has some limitations.…”

Section: Discussionmentioning

confidence: 99%

Resting heart rate and incident heart failure and cardiovascular mortality in older adults: role of inflammation and endothelial dysfunction: the PROSPER study

Nanchen

Stott

Gussekloo

et al. 2013

European J of Heart Fail

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AimsResting heart rate is a promising modifiable cardiovascular risk marker in older adults, but the mechanisms linking heart rate to cardiovascular disease are not fully understood. We aimed to assess the association between resting heart rate and incident heart failure (HF) and cardiovascular mortality, and to examine whether these associations might be attributable to systemic inflammation and endothelial dysfunction. Methods and resultsWe studied 4084 older adults aged 70-82 years with known cardiovascular risk factors or previous cardiovascular disease, without pre-existing HF or beta-blockers in the PROSPER study. Over a 3.2-year follow-up period, we examined incident HF hospitalization and cardiovascular mortality according to resting heart rate, along with C-reactive protein (CRP), interleukin-6 (IL-6), tissue plasminogen activator (tPA), and von Willebrand factor (vWf). Mean heart rate was 67 b.p.m. for men and 70 b.p.m. for women. CRP, IL-6, tPA, and vWf levels were all positively correlated with heart rate. After multivariate adjustment, heart rate was associated with HF hospitalization [hazard ratio (HR) 1.78 for highest vs. lowest distribution third, 95% confidence interval (CI) 1.21-2.63, P ¼ 0.003] and cardiovascular mortality (HR 1.74, 95% CI 1.23-2.47, P ¼ 0.002). Further adjustment for both IL-6 and vWf levels decreased HR to 1.60 (95% CI 1.08-2.38, P ¼ 0.020) for HF and to 1.50 (95% CI 1.04-2.15, P ¼ 0.028) for cardiovascular mortality. ConclusionIncreased heart rate is associated with increased systemic inflammation and endothelial dysfunction. These factors are likely to contribute to, but do not fully explain, the risk of HF and cardiovascular death associated with increased heart rate in older age.--

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“…By comparison, in SHRs (spontaneously hypertensive rats), 2 weeks of pravastatin [100 mg/l (in drinking water)], a hydrophilic statin, did not alter plasma cholesterol or BP, but reduced HR [74]. An accompanying in vitro study of the right atrium found that pravastatin diminished the release of pre-loaded tracerlabelled [ 3 H]-NE to that of the WKY control rats.…”

Section: Hypertensionmentioning

confidence: 98%

Statins and the autonomic nervous system

Millar

Floras

2013

Clinical Science

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Statins (3-hydroxy-3-methylglutaryl-CoA reductase inhibitors) reduce plasma cholesterol and improve endothelium-dependent vasodilation, inflammation and oxidative stress. A 'pleiotropic' property of statins receiving less attention is their effect on the autonomic nervous system. Increased central sympathetic outflow and diminished cardiac vagal tone are disturbances characteristic of a range of cardiovascular conditions for which statins are now prescribed routinely to reduce cardiovascular events: following myocardial infarction, and in hypertension, chronic kidney disease, heart failure and diabetes. The purpose of the present review is to synthesize contemporary evidence that statins can improve autonomic circulatory regulation. In experimental preparations, high-dose lipophilic statins have been shown to reduce adrenergic outflow by attenuating oxidative stress in central brain regions involved in sympathetic and parasympathetic discharge induction and modulation. In patients with hypertension, chronic kidney disease and heart failure, lipophilic statins, such as simvastatin or atorvastatin, have been shown to reduce MNSA (muscle sympathetic nerve activity) by 12-30%. Reports concerning the effect of statin therapy on HRV (heart rate variability) are less consistent. Because of their implications for BP (blood pressure) control, insulin sensitivity, arrhythmogenesis and sudden cardiac death, these autonomic nervous system actions should be considered additional mechanisms by which statins lower cardiovascular risk.

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Pravastatin normalises peripheral cardiac sympathetic hyperactivity in the spontaneously hypertensive rat

Cited by 36 publications

References 36 publications

Influence and Pathophysiological Mechanisms of Simvastatin on Prostatic Hyperplasia in Spontaneously Hypertensive Rats

Influence and Pathophysiological Mechanisms of Simvastatin on Prostatic Hyperplasia in Spontaneously Hypertensive Rats

Resting heart rate and incident heart failure and cardiovascular mortality in older adults: role of inflammation and endothelial dysfunction: the PROSPER study

Statins and the autonomic nervous system

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